Famoxadone: the discovery and optimisation of a new agricultural fungicide

Famoxadone (3-anilino-5-methyl-5-(4-phenoxyphenyl)-1,3-oxazolidine-2,4-dione), is a new agricultural fungicide recently commercialized by DuPont under the trade name Famoxate. Famoxadone is a member of a new class of oxazolidinone fungicides that demonstrate excellent control of plant pathogens in the Ascomycete, Basidiomycete, and Oomycete classes that infect grapes, cereals, tomatoes, potatoes and other crops. DuPont's entry into the oxazolidinone area resulted from the procurement of 5-methyl-5-phenyl-3-phenylamino-2-thioxo-4-oxazolidinone (1) from Professor Detlef Geffken, then at the University of Bonn. An extensive analog program was initiated immediately after the fungicidal activity of 1 was discovered through routine greenhouse testing. The discovery program in the oxazolidinone area eventually culminated in the advancement of famoxadone to commercial development in the early 1990s. The synthesis of various oxazolidinone ring systems and the development of the structure-activity relationships that led to the discovery of famoxadone are described.